FDA warns another Indian drug maker on serious quality control lapses

et another Indian drug manufacturer was reprimanded by US regulators for a variety of serious quality-control infractions. But this particular episode may resonate wider than most because the company also makes products for still other manufacturers, but failed to notify them of the problems.

And the problems were extensive. The US Food and Drug Administration cited Sri Krishna Pharmaceuticals for numerous issues concerning data integrity that involved laboratory records, computer systems, validating processes, and manipulating records of batches of drugs.

Overall, the FDA said Sri Krishna failed to establish adequate written procedures to assure manufactured drugs have the stated strength, quality, and purity. The agency found the violations during a December 2014 inspection, but the company failed to sufficiently correct the problems, according to an April 1 warning letter that was sent to the drug maker and posted this week on the FDA web site.

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Among the infractions: the company was destroying original batch records and then backdated replacements pages that were approved by quality and production managers. And lab records did not contain all of the raw data generated during testing for finished drugs, which meant the quality control unit relied on incomplete records to decide which batches to release for regulatory reviews.

In one instance, a quality-control analyst deleted original data generated during testing used to validate products and admitted plans to fabricate sample preparation data.

Moreover, the company shipped certain batches of product to the United States that were made with an invalid process with new equipment. Sri Krishna makes various products at the facility, including the acetaminophen pain reliever and the metformin diabetes treatment, according to its web site.

“The inspection process is mostly based on review of company records, but what was going on when FDA was not there?” said John English, a pharmaceutical industry consultant who specializes in computer system validation. “If you cannot trust the accuracy of the records, then the question becomes: Is this data science or science fiction?”

Sri Krishna could not be reached for comment. The Italian Medicines Agency late last year, by the way, issued its own warning to the company over manufacturing problems.

The violations are problematic not just for Sri Krishna, though, but also for other drug makers that rely on the company to manufacture some of its products, according to Vince Suneja who heads TwoFour Insight Group, a consulting firm that advises Indian drug makers.

“Most importantly, the FDA noted that there is no evidence that Krishna informed its customers of these and any other significant problems and/or discrepancies encountered,” he wrote in a note to clients. “Ultimately, Krishna’s customers that are using the company as their contract manufacturer may be impacted most significantly by the warning letter.”

As we have noted previously, this is only the latest instance in which the FDA has scolded an Indian drug maker or ingredients supplier for quality control problems. Over the past several years, in fact, there has been mounting concern over the safety of the pharmaceutical supply chain after the agency cited several companies for production failures. For their part, Indian drug makers complain of undue scrutiny.

The FDA has tried to bolster oversight to address the problem. In fact, Suneja noted that the warning letter mirrors various points that the FDA raised just last week in a new draft guidance that was issued to advise drug makers on how to ensure they comply with so-called good manufacturing practices. In particular, the guidance focuses on record keeping and data.

The guidance “provides a shot over the bow to alert firms that FDA is watching, and firms need to step up to the plate and take affirmative action in-house to assure the integrity of its records and data, and how they are maintained,” according to a blog post by Robert Pollock, a former acting deputy director of the FDA Office of Generic Drugs, who now works at Lachman Consultants and advises drug makers.

This is appauling; however, not a surprise. It is imperative that adequate vendor qualification be conducted not only prior to the utilization of any third parties products or services but also ongoing throughout the conduct of these operations. Furthermore, firms operating in our industry need to understand that it is ultimately their responsibility to ensure that the products/services outsourced are what they purport to be and produced under a validated and verifiably compliant quality management system. While the business mind might only see this as a means of reducing production cost, the cost of non compliance and risk to the overall integrity of the product and, most importantly, the patients use of the product, out ways any “assumed profit margin increase” that could have been the rationale for outsourcing to a firm with a history of noncompliance. I am a proud regulatory compliance expert but my entrance into the love of navigating the Regulatory pipeline came out of my being a scientist and product entrepreneur first. Compliance it’s not just the law, it’s also good business. I challenge my colleagues and any opposition to take this whole heartedly and advance the standard rather than take the risk and be yet another statistic.